Prostaglandins are naturally occurring 20-carbon fatty acid derivatives produced by the oxidative metabolism of fatty acids (e.g., arachidonic acid). They and their non-naturally occurring analogs (which together can be referred to as prostanoids) have a wide variety of therapeutic uses.
Prostaglandins typically include at least one five-membered ring. For example, PGFα prostaglandins and prostaglandin analogs can comprise a cyclopentyl ring carrying two hydroxyl groups in a cis configuration and two side chains in a trans configuration. The side chains can contain double bonds and a variety of substituents. They have therapeutic value in several indications including, but not limited to, glaucoma, ocular hypertension, ulcers, and inducing or accelerating labor.
Bimatoprost, an exemplary PGFα prostaglandin analog, is sold in the U.S., Canada, and Europe by Allergan under the trade name LUMIGAN™ (Allergan, Inc., Irvine, Calif., United States of America) for use topically as eye drops to control the progression of glaucoma and in the management of ocular hypertension. It reduces intraocular pressure by increasing the outflow of aqueous fluid from the eyes. In December 2008, the U.S. Food and Drug Administration approved a cosmetic formulation of bimatoprost, sold under the trade name LATISSE™ (Allergan, Inc., Irvine, Calif., United States of America) for use as a treatment for inadequate eyelash growth. It has further been suggested that bimatoprost has the ability to reduce adipose (fat) tissue.
A variety of methods for synthesizing PGFα and other prostaglandins and prostaglandin analogs are known. See e.g., International Publication No. WO 2005/058812 to Clissold et al., WO 02/096868, WO 02/090324, Chem. Rev. (1993, vol. 93, pages 1533 1564), Chinese Journal of Medicinal Chemistry (1998, vol. 36, pages 213-217), and the references cited therein. However, there remains a need in the art for additional methods of synthesizing prostanoids, such as but not limited to more versatile and efficient methods.